10-48405106-GATATATAT-GATATATATATATATAT

Variant names:

• chr10-48405106-G-GATATATAT
• rs10657070
• NM_001323329.2:c.252+140_252+147dupATATATAT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001323329.2(MAPK8):​c.252+140_252+147dupATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00529 in 90,590 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.021 (23 hom., cov: 0)
  • Exomes 𝑓: 0.0053 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MAPK8 NM_001323329.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163
• Publications: 1 publications found

Genes affected

MAPK8 (HGNC:6881): (mitogen-activated protein kinase 8) The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. This kinase is activated by various cell stimuli, and targets specific transcription factors, and thus mediates immediate-early gene expression in response to cell stimuli. The activation of this kinase by tumor-necrosis factor alpha (TNF-alpha) is found to be required for TNF-alpha induced apoptosis. This kinase is also involved in UV radiation induced apoptosis, which is thought to be related to cytochrom c-mediated cell death pathway. Studies of the mouse counterpart of this gene suggested that this kinase play a key role in T cell proliferation, apoptosis and differentiation. Several alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Apr 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001323329.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8	NM_001323329.2	MANE Select	c.252+140_252+147dupATATATAT		intron	N/A	NP_001310258.1	P45983-1
	MAPK8	NM_001278547.2		c.252+140_252+147dupATATATAT		intron	N/A	NP_001265476.1	A1L4K2
	MAPK8	NM_001323322.2		c.252+140_252+147dupATATATAT		intron	N/A	NP_001310251.1	P45983-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MAPK8	ENST00000374189.6	TSL:5 MANE Select	c.252+125_252+126insATATATAT		intron	N/A	ENSP00000363304.1	P45983-1
	MAPK8	ENST00000374176.8	TSL:1	c.252+125_252+126insATATATAT		intron	N/A	ENSP00000363291.4	P45983-4
	MAPK8	ENST00000374179.8	TSL:1	c.252+125_252+126insATATATAT		intron	N/A	ENSP00000363294.3	P45983-3

Frequencies

GnomAD3 genomes AF: 0.0205 AC: 2966 AN: 144404 Hom.: 23 Cov.: 0

Gnomad AFR AF: 0.0200

Gnomad AMI AF: 0.0210

Gnomad AMR AF: 0.0181

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.00995

Gnomad FIN AF: 0.0172

Gnomad MID AF: 0.0270

Gnomad NFE AF: 0.0235

Gnomad OTH AF: 0.0277

GnomAD4 exome AF: 0.00529 AC: 479 AN: 90590 Hom.: 0 AF XY: 0.00560 AC XY: 272 AN XY: 48602

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00324 AC: 9 AN: 2778

American (AMR) AF: 0.00410 AC: 14 AN: 3418

Ashkenazi Jewish (ASJ) AF: 0.00370 AC: 10 AN: 2704

East Asian (EAS) AF: 0.00 AC: 0 AN: 6266

South Asian (SAS) AF: 0.000705 AC: 2 AN: 2838

European-Finnish (FIN) AF: 0.00582 AC: 53 AN: 9100

Middle Eastern (MID) AF: 0.00508 AC: 2 AN: 394

European-Non Finnish (NFE) AF: 0.00645 AC: 371 AN: 57556

Other (OTH) AF: 0.00325 AC: 18 AN: 5536

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0205 AC: 2968 AN: 144466 Hom.: 23 Cov.: 0 AF XY: 0.0201 AC XY: 1413 AN XY: 70174

African (AFR) AF: 0.0200 AC: 795 AN: 39768

American (AMR) AF: 0.0181 AC: 264 AN: 14618

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 96 AN: 3364

East Asian (EAS) AF: 0.000200 AC: 1 AN: 4990

South Asian (SAS) AF: 0.00998 AC: 45 AN: 4508

European-Finnish (FIN) AF: 0.0172 AC: 147 AN: 8542

Middle Eastern (MID) AF: 0.0292 AC: 8 AN: 274

European-Non Finnish (NFE) AF: 0.0235 AC: 1539 AN: 65546

Other (OTH) AF: 0.0275 AC: 55 AN: 2000

Alfa AF: 0.00624 Hom.: 648

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10657070; hg19: chr10-49613149;